沙库巴曲缬沙坦治疗心力衰竭的研究进展
Research Progress on Sacubitril/Valsartan in the Treatment of Heart Failure
摘要: 心力衰竭药物治疗领域近年迎来重大范式革新，其中血管紧张素受体脑啡肽酶抑制剂(ARNI)代表药物沙库巴曲缬沙坦通过双重神经激素调控机制，显著改写了射血分数降低型心力衰竭(HFrEF)的治疗格局。基于里程碑式临床研究证据，该药物已被确立为HFrEF核心治疗方案。本文旨对沙库巴曲缬沙坦在心力衰竭领域的重大研究进展及未来的研究方向等进行解读和总结。
Abstract: The field of pharmacotherapy for heart failure has recently witnessed a major paradigm shift. Sacubitril/valsartan, a representative angiotensin receptor-neprilysin inhibitor (ARNI), has significantly transformed the treatment paradigm for heart failure with reduced ejection fraction (HFrEF) through its dual neurohormonal modulation mechanism. Supported by landmark clinical evidence, this agent has been established as a cornerstone therapy for HFrEF. This review aims to interpret and summarize key research advances and future directions regarding sacubitril/valsartan in the management of heart failure.
文章引用：张玺, 员峰莉. 沙库巴曲缬沙坦治疗心力衰竭的研究进展[J]. 临床医学进展, 2025, 15(9): 1649-1655. https://doi.org/10.12677/acm.2025.1592666

参考文献

[1] Virani, S.S., Alonso, A., Benjamin, E.J., et al. (2020) Heart Disease and Stroke Statistics-2020 Update: A Report from the American Heart Association. Circulation, 141, e139-e596. [Google Scholar] [CrossRef] 
[2] James, S.L., Abate, D., Abate, K.H., et al. (2018) Global, Regional, and National Incidence, Prevalence, and Years Lived with Disability for 354 Diseases and Injuries for 195 Countries and Territories, 1990-2017: A Systematic Analysis for the Global Burden of Disease Study 2017. The Lancet, 392, 1789-1858. [Google Scholar] [CrossRef] 
[3] Savarese, G., Becher, P.M., Lund, L.H., Seferovic, P., Rosano, G.M.C. and Coats, A.J.S. (2022) Global Burden of Heart Failure: A Comprehensive and Updated Review of Epidemiology. Cardiovascular Research, 118, 3272-3287. [Google Scholar] [CrossRef] [PubMed]
[4] Dunlay, S.M., Redfield, M.M., Weston, S.A., Therneau, T.M., Hall Long, K., Shah, N.D., et al. (2009) Hospitalizations after Heart Failure Diagnosis. Journal of the American College of Cardiology, 54, 1695-1702. [Google Scholar] [CrossRef] [PubMed]
[5] Butler, J., Yang, M., Manzi, M.A., Hess, G.P., Patel, M.J., Rhodes, T., et al. (2019) Clinical Course of Patients with Worsening Heart Failure with Reduced Ejection Fraction. Journal of the American College of Cardiology, 73, 935-944. [Google Scholar] [CrossRef] [PubMed]
[6] Gu, J., Noe, A., Chandra, P., Al‐Fayoumi, S., Ligueros‐Saylan, M., Sarangapani, R., et al. (2010) Pharmacokinetics and Pharmacodynamics of LCZ696, a Novel Dual‐Acting Angiotensin Receptor—Neprilysin Inhibitor (ARNi). The Journal of Clinical Pharmacology, 50, 401-414. [Google Scholar] [CrossRef] [PubMed]
[7] Mangiafico, S., Costello-Boerrigter, L.C., Andersen, I.A., Cataliotti, A. and Burnett, J.C. (2012) Neutral Endopeptidase Inhibition and the Natriuretic Peptide System: An Evolving Strategy in Cardiovascular Therapeutics. European Heart Journal, 34, 886-893. [Google Scholar] [CrossRef] [PubMed]
[8] Polhemus, D.J., Trivedi, R.K., Gao, J., Li, Z., Scarborough, A.L., Goodchild, T.T., et al. (2017) Renal Sympathetic Denervation Protects the Failing Heart via Inhibition of Neprilysin Activity in the Kidney. Journal of the American College of Cardiology, 70, 2139-2153. [Google Scholar] [CrossRef] [PubMed]
[9] Mollace, V., Gliozzi, M., Capuano, A. and Rossi, F. (2017) Modulation of Raas-Natriuretic Peptides in the Treatment of HF: Old Guys and Newcomers. International Journal of Cardiology, 226, 126-131. [Google Scholar] [CrossRef] [PubMed]
[10] Almufleh, A., Marbach, J., Chih, S., et al. (2017) Ejection Fraction Improvement and Reverse Remodeling Achieved with Sacubitril/Valsartan in Heart Failure with Reduced Ejection Fraction Patients. American Journal of Cardiovascular Disease, 7, 108-113.
[11] Jessup, M., Fox, K.A.A., Komajda, M., McMurray, J.J.V. and Packer, M. (2014) PARADIGM-HF—The Experts’ Discussion. New England Journal of Medicine, 371, e15. [Google Scholar] [CrossRef] [PubMed]
[12] Mogensen, U.M., Køber, L., Kristensen, S.L., Jhund, P.S., Gong, J., Lefkowitz, M.P., et al. (2017) The Effects of Sacubitril/Valsartan on Coronary Outcomes in PARADIGM-HF. American Heart Journal, 188, 35-41. [Google Scholar] [CrossRef] [PubMed]
[13] Solomon, S.D., McMurray, J.J.V., Anand, I.S., Ge, J., Lam, C.S.P., Maggioni, A.P., et al. (2019) Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. New England Journal of Medicine, 381, 1609-1620. [Google Scholar] [CrossRef] [PubMed]
[14] Vaduganathan, M., Mentz, R.J., Claggett, B.L., Miao, Z.M., Kulac, I.J., Ward, J.H., et al. (2023) Sacubitril/Valsartan in Heart Failure with Mildly Reduced or Preserved Ejection Fraction: A Pre-Specified Participant-Level Pooled Analysis of PARAGLIDE-HF and PARAGON-HF. European Heart Journal, 44, 2982-2993. [Google Scholar] [CrossRef] [PubMed]
[15] Solomon, S.D., Zile, M., Pieske, B., Voors, A., Shah, A., Kraigher-Krainer, E., et al. (2012) The Angiotensin Receptor Neprilysin Inhibitor LCZ696 in Heart Failure with Preserved Ejection Fraction: A Phase 2 Double-Blind Randomised Controlled Trial. The Lancet, 380, 1387-1395. [Google Scholar] [CrossRef] [PubMed]
[16] Ruilope, L.M., Dukat, A., Böhm, M., Lacourcière, Y., Gong, J. and Lefkowitz, M.P. (2010) Blood-Pressure Reduction with LCZ696, a Novel Dual-Acting Inhibitor of the Angiotensin II Receptor and Neprilysin: A Randomised, Double-Blind, Placebo-Controlled, Active Comparator Study. The Lancet, 375, 1255-1266. [Google Scholar] [CrossRef] [PubMed]
[17] Supasyndh, O., Sun, N., Kario, K., Hafeez, K. and Zhang, J. (2016) Long-Term (52-Week) Safety and Efficacy of Sacubitril/Valsartan in Asian Patients with Hypertension. Hypertension Research, 40, 472-476. [Google Scholar] [CrossRef] [PubMed]
[18] Cheung, D.G., Aizenberg, D., Gorbunov, V., Hafeez, K., Chen, C. and Zhang, J. (2018) Efficacy and Safety of Sacubitril/Valsartan in Patients with Essential Hypertension Uncontrolled by Olmesartan: A Randomized, Double‐Blind, 8‐Week Study. The Journal of Clinical Hypertension, 20, 150-158. [Google Scholar] [CrossRef] [PubMed]
[19] Li, W., Gong, M., Yu, Q., Liu, R., Chen, K., Lv, W., et al. (2022) Efficacy of Angiotensin Receptor Neprilysin Inhibitor in Asian Patients with Refractory Hypertension. The Journal of Clinical Hypertension, 24, 449-456. [Google Scholar] [CrossRef] [PubMed]
[20] Haynes, R., Judge, P.K., Staplin, N., Herrington, W.G., Storey, B.C., Bethel, A., et al. (2018) Effects of Sacubitril/Valsartan versus Irbesartan in Patients with Chronic Kidney Disease: A Randomized Double-Blind Trial. Circulation, 138, 1505-1514. [Google Scholar] [CrossRef] [PubMed]
[21] Damman, K., Gori, M., Claggett, B., Jhund, P.S., Senni, M., Lefkowitz, M.P., et al. (2018) Renal Effects and Associated Outcomes during Angiotensin-Neprilysin Inhibition in Heart Failure. JACC: Heart Failure, 6, 489-498. [Google Scholar] [CrossRef] [PubMed]
[22] Mc Causland, F.R., Lefkowitz, M.P., Claggett, B., Packer, M., Senni, M., Gori, M., et al. (2022) Angiotensin-Neprilysin Inhibition and Renal Outcomes across the Spectrum of Ejection Fraction in Heart Failure. European Journal of Heart Failure, 24, 1591-1598. [Google Scholar] [CrossRef] [PubMed]
[23] Curtain, J.P., Jackson, A.M., Shen, L., Jhund, P.S., Docherty, K.F., Petrie, M.C., et al. (2022) Effect of Sacubitril/Valsartan on Investigator‐Reported Ventricular Arrhythmias in PARADIGM‐HF. European Journal of Heart Failure, 24, 551-561. [Google Scholar] [CrossRef] [PubMed]
[24] McMurray, J.J.V., Packer, M., Desai, A.S., Gong, J., Lefkowitz, M.P., Rizkala, A.R., et al. (2014) Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure. New England Journal of Medicine, 371, 993-1004. [Google Scholar] [CrossRef] [PubMed]
[25] Rosano, G.M.C., Tamargo, J., Kjeldsen, K.P., Lainscak, M., Agewall, S., Anker, S.D., et al. (2018) Expert Consensus Document on the Management of Hyperkalaemia in Patients with Cardiovascular Disease Treated with Renin Angiotensin Aldosterone System Inhibitors: Coordinated by the Working Group on Cardiovascular Pharmacotherapy of the European Society of Cardiology. European Heart Journal—Cardiovascular Pharmacotherapy, 4, 180-188. [Google Scholar] [CrossRef] [PubMed]
[26] Docherty, K.F., Vaduganathan, M., Solomon, S.D. and McMurray, J.J.V. (2020) Sacubitril/Valsartan. JACC: Heart Failure, 8, 800-810. [Google Scholar] [CrossRef] [PubMed]
[27] Savarese, G., Stolfo, D., Sinagra, G. and Lund, L.H. (2021) Heart Failure with Mid-Range or Mildly Reduced Ejection Fraction. Nature Reviews Cardiology, 19, 100-116. [Google Scholar] [CrossRef] [PubMed]
[28] Damman, K. and Testani, J.M. (2015) The Kidney in Heart Failure: An Update. European Heart Journal, 36, 1437-1444. [Google Scholar] [CrossRef] [PubMed]
[29] Ibrahim, N.E., Song, Y., Cannon, C.P., Doros, G., Russo, P., Ponirakis, A., et al. (2019) Heart Failure with Mid‐Range Ejection Fraction: Characterization of Patients from the PINNACLE Registry®. ESC Heart Failure, 6, 784-792. [Google Scholar] [CrossRef] [PubMed]

为你推荐